In utero detection of T7 phage after systemic administration to pregnant mice

Abstract Through drinking water, humans are commonly exposed to atrazine, a herbicide that acts as an endocrine and metabolic disruptor. It interferes with steroidogenesis, including promoting oestrogen production and altering cell metabolism. However, its precise impact on uterine development remains unknown. This study aimed to determine the effect of prolonged atrazine exposure on the uterus. Pregnant mice (n = 5/group) received 5 mg/kg body weight/day atrazine or DMSO in drinking water from gestational day 9.5 until weaning. Offspring continued to be exposed until 3 or 6 months of age (n = 5–9/group), when uteri were collected for morphological and molecular analyses and steroid quantification. Endometrial hyperplasia and leiomyoma were evident in the uteri of atrazine-exposed mice. Uterine oestrogen concentration, oestrogen receptor expression, and localisation were similar between groups, at both ages (P > 0.1). The expression and localisation of key epithelial-to-mesenchymal transition (EMT) genes and proteins, critical for tumourigenesis, remained unchanged between treatments, at both ages (P > 0.1). Hence, oestrogen-mediated changes to established EMT markers do not appear to underlie abnormal uterine morphology evident in atrazine exposure mice. This is the first report of abnormal uterine morphology following prolonged atrazine exposure starting in utero, it is likely that the abnormalities identified would negatively affect female fertility, although mechanisms remain unknown and require further study.

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Vertebral malformation in the mouse foetus caused by X-radiation of the mother during pregnancy

Development ◽

10.1242/dev.12.4.841 ◽

1964 ◽

Vol 12 (4) ◽

pp. 841-850

Author(s):

Ujihiro Murakami ◽

Yoshiro Kameyama

Keyword(s):

Early Pregnancy ◽

Vertebral Column ◽

Strain Differences ◽

In Utero ◽

Oxygen Deprivation ◽

Experimental Animals ◽

Vertebral Malformation ◽

Pregnant Mice ◽

Maternal Hypoxia ◽

In Pregnancy

Maternal hypoxia in early pregnancy can result in malformations of the vertebrae of mouse foetuses, and there is a tendency for more posterior vertebrae to be affected the later in pregnancy the oxygen deprivation occurs (Murakami & Kameyama, 1963). Ingalls et al. (1957) and Degenhardt (1954, 1959) had earlier obtained similar results. We have also exposed pregnant mice to X-radiation and studied the consequent malformations. The effects on the extremities have already been described (Murakami, Kameyama & Nogami, 1963), and in the present paper we shall describe the effects on the vertebral column. Vertebral malformations in animals irradiated in utero have been described by Job, Leibold & Fitzmaurice (1935), Warkany and Schraffenberger (1947), Russell. (1950, 1954), and Russell & Russell (1954). In order to obtain results comparable with those of our experiments with hypoxia, no less than to detect inter-strain differences, we used mice of the ddN and CF1 strains originally supplied by the Central Laboratories for Experimental Animals, Tokyo (Zikkendobutsu Chuo Kenkyujo).

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In Utero Exposure to Environmental Tobacco Smoke Increases Neuroinflammation in Offspring

Frontiers in Toxicology ◽

10.3389/ftox.2021.802542 ◽

2022 ◽

Vol 3 ◽

Author(s):

Ana Carolina Cardoso dos Santos Durão ◽

Wesley Nogueira Brandão ◽

Vitor Bruno ◽

Lídia Emmanuela W. Spelta ◽

Stephanie de Oliveira Duro ◽

...

Keyword(s):

Environmental Tobacco Smoke ◽

Tobacco Smoke ◽

Embryo Implantation ◽

Sudden Infant Death ◽

In Utero ◽

Sudden Infant ◽

Mixed Cell ◽

Necrosis Factor Alpha ◽

Lps Challenge ◽

Pregnant Mice

The embryonic stage is the most vulnerable period for congenital abnormalities. Due to its prolonged developmental course, the central nervous system (CNS) is susceptible to numerous genetic, epigenetic, and environmental influences. During embryo implantation, the CNS is more vulnerable to external influences such as environmental tobacco smoke (ETS), increasing the risk for delayed fetal growth, sudden infant death syndrome, and immune system abnormalities. This study aimed to evaluate the effects of in utero exposure to ETS on neuroinflammation in the offspring of pregnant mice challenged or not with lipopolysaccharide (LPS). After the confirmation of mating by the presence of the vaginal plug until offspring birth, pregnant C57BL/6 mice were exposed to either 3R4F cigarettes smoke (Kentucky University) or compressed air, twice a day (1h each), for 21 days. Enhanced glial cell and mixed cell cultures were prepared from 3-day-old mouse pups. After cell maturation, both cells were stimulated with LPS or saline. To inhibit microglia activation, minocycline was added to the mixed cell culture media 24 h before LPS challenge. To verify the influence of in utero exposure to ETS on the development of neuroinflammatory events in adulthood, a different set of 8-week-old animals was submitted to the Autoimmune Experimental Encephalomyelitis (EAE) model. The results indicate that cells from LPS-challenged pups exposed to ETS in utero presented high levels of proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNFα) and decreased cell viability. Such a proinflammatory environment could modulate fetal programming by an increase in microglia and astrocytes miRNA155. This scenario may lead to the more severe EAE observed in pups exposed to ETS in utero.

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Treatment with constitutive androstane receptor ligand during pregnancy prevents insulin resistance in offspring from high-fat diet-induced obese pregnant mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00167.2012 ◽

2012 ◽

Vol 303 (2) ◽

pp. E293-E300 ◽

Cited By ~ 16

Author(s):

Hisashi Masuyama ◽

Yuji Hiramatsu

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Control Diet ◽

Constitutive Androstane Receptor ◽

In Utero ◽

High Fat ◽

Adiponectin Mrna ◽

Genes Encoding ◽

Pregnant Mice ◽

And Control

The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance even during pregnancy, while exposure to a high-fat diet (HFD) in utero in mice can induce a type 2 diabetes phenotype that can be transmitted to the progeny. Therefore, we examined whether treatment with a CAR ligand during pregnancy could prevent hypertension, insulin resistance, and hyperlipidemia in the offspring from HFD-induced obese pregnant mice (OH mice). We employed four groups of offspring from HFD-fed and control diet-fed pregnant mice with or without treatment with a CAR ligand. Treatment with a CAR ligand during pregnancy improved glucose tolerance and the levels of triglyceride and adipocytokine and restored the changes induced by HFD with amelioration of hypertension in the adult OH mice. This treatment also increased adiponectin mRNA expression, suppressed leptin expression in adipose tissues of OH mice, and abolished the effect of HFD on the epigenetic modifications of the genes encoding adiponectin and leptin in the offspring during immaturity and adulthood. Our data suggest that CAR might be a potential therapeutic target to prevent metabolic syndrome in adulthood of offspring exposed to an HFD in utero.

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Maternal vaccination and protective immunity against Zika virus vertical transmission

Nature Communications ◽

10.1038/s41467-019-13589-1 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 9

Author(s):

Chao Shan ◽

Xuping Xie ◽

Huanle Luo ◽

Antonio E. Muruato ◽

Yang Liu ◽

...

Keyword(s):

Zika Virus ◽

Protective Immunity ◽

Neutralizing Antibody ◽

In Utero ◽

Pregnant Mouse ◽

T Cell Response ◽

Zikv Infection ◽

Maternal Immunization ◽

Maternal Vaccination ◽

Pregnant Mice

AbstractAn important goal of the Zika virus (ZIKV) vaccine is to prevent a congenital syndrome in fetuses of pregnant women, but studies directly evaluating maternal vaccination for ZIKV are lacking. Here we report maternal vaccination using a live-attenuated ZIKV vaccine (3ʹUTR-∆10-LAV) in a pregnant mouse model. Maternal immunization with 3ʹUTR-∆10-LAV does not cause any adverse effects on pregnancy, fetal development, or offspring behavior. One maternal immunization fully protects dams against ZIKV infection and in utero transmission. Although neutralizing antibody alone is sufficient to prevent in utero transmission, a higher neutralizing titer is required to protect pregnant mice against in utero transmission than that required to protect non-pregnant mice against viral infection. The immunized dams transfer maternal antibodies to pups, which protect neonates against ZIKV infection. Notably, pregnancy weakens maternal T cell response to 3ʹUTR-∆10-LAV vaccination. Our results suggest that, besides vaccinating non-pregnant individuals, 3ʹUTR-∆10-LAV may also be considered for maternal vaccination.

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Intrauterine exposure to low-dose DBP in the mice induces obesity in offspring via suppression of UCP1 mediated ER stress

Scientific Reports ◽

10.1038/s41598-020-73477-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Huan Li ◽

Jianqiao Li ◽

Zhenting Qu ◽

Honghao Qian ◽

Jing Zhang ◽

...

Keyword(s):

Er Stress ◽

Serum Lipids ◽

Low Dose ◽

Corn Oil ◽

In Utero ◽

Standard Diet ◽

Intrauterine Exposure ◽

Adipose Tissue Weight ◽

Pregnant Mice ◽

Lower Expression

Abstract Dibutyl phthalate (DBP) is recognized as an environmental endocrine disruptor that has been detected in fetal and postnatal samples. Recent evidence found that in utero DBP exposure was associated with an increase of adipose tissue weight and serum lipids in offspring, but the precise mechanism is unknown. Here we aimed to study the effects of in utero DBP exposure on obesity in offspring and examine possible mechanisms. SPF C57BL/6J pregnant mice were gavaged with either DBP (5 mg /kg/day) or corn oil, from gestational day 12 until postnatal day 7. After the offspring were weaned, the mice were fed a standard diet for 21 weeks, and in the last 2 weeks 20 mice were selected for TUDCA treatment. Intrauterine exposure to low-dose DBP promoted obesity in offspring, with evidence of glucose and lipid metabolic disorders and a decreased metabolic rate. Compared to controls, the DBP exposed mice had lower expression of UCP1 and significantly higher expression of Bip and Chop, known markers of endoplasmic reticulum (ER) stress. However, TUDCA treatment of DBP exposed mice returned these parameters nearly to the levels of the controls, with increased expression of UCP1, lower expression of Bip and Chop and ameliorated obesity. Intrauterine exposure of mice to low-dose DBP appears to promote obesity in offspring by inhibiting UCP1 via ER stress, a process that was largely reversed by treatment with TUDCA.

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Lymphoma and lung cancer in offspring born to pregnant mice dosed with dibenzo[a,l]pyrene: The importance of in utero vs. lactational exposure

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2008.09.009 ◽

2008 ◽

Vol 233 (3) ◽

pp. 454-458 ◽

Cited By ~ 25

Author(s):

David J. Castro ◽

Christiane V. Löhr ◽

Kay A. Fischer ◽

Clifford B. Pereira ◽

David E. Williams

Keyword(s):

Lung Cancer ◽

In Utero ◽

Lactational Exposure ◽

Pregnant Mice ◽

Cancer In Offspring

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Systemic administration of the glutamate agonist L-cysteine produces CNS changes, mimicking hypoxic-ischemic damage in fetal rats, in utero

Journal of the Society for Gynecologic Investigation ◽

10.1016/1071-5576(95)94526-z ◽

1995 ◽

Vol 2 (2) ◽

pp. 349

Author(s):

R BALL

Keyword(s):

In Utero ◽

Systemic Administration ◽

Ischemic Damage ◽

Fetal Rats

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Mesoporous silica nanoparticle is comparatively safer than zinc oxide nanoparticle which can cause profound steroidogenic effects on pregnant mice and male offspring exposed in utero

Toxicology and Industrial Health ◽

10.1177/0748233718757641 ◽

2018 ◽

Vol 34 (8) ◽

pp. 507-524 ◽

Cited By ~ 4

Author(s):

Nisha Bara ◽

M Eshwarmoorthy ◽

Kesavan Subaharan ◽

Gautam Kaul

Keyword(s):

Zinc Oxide ◽

Mesoporous Silica ◽

Mesoporous Silica Nanoparticles ◽

Animal Health ◽

Serum Testosterone ◽

Treated Group ◽

In Utero ◽

Male Offspring ◽

Zno Nps ◽

Pregnant Mice

The increasing use of nanomaterials has naturally caused heightened concerns about their potential risks to human and animal health. We investigated the effect of zinc oxide nanoparticles (ZnO NPs) and mesoporous silica nanoparticles (MSN) on steroidogenesis in the corpus luteum (CL) of pregnant mice and testis of male offspring. Pregnant albino mice were exposed to ZnO NPs and MSN for 2 days on alternate days, gestation days 15–19. Hepatic injury marker enzymes increased in the higher concentration of NM-exposed mother mice, but histological examination revealed no changes in the placenta of pregnant mice, whereas testis of male offspring showed gross pathological changes. The expression pattern of progesterone biosynthesis-related genes was also altered in the CL of NP-exposed pregnant mice. In utero exposure of ZnO NPs increased the relative expression of StAR in 100 mg/kg body weight (BW) ZnO NP-treated and bulk ZnO-treated groups and P450 side-chain cleavage enzyme (P450scc) in 50 mg/kg BW ZnO NP-treated and 100 mg/kg of bulk ZnO-treated male offspring. Serum testosterone concentration significantly increased in the 100 mg/kg of bulk ZnO-treated group and decreased in the 250 mg/kg of MSN-treated group and a single dose of 300 mg/Kg BW of ZnO NPs caused miscarriages and adversely affected the developing foetus in mice.

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In Utero Exposure to Simulated Complex Urban Air Pollution Disturbs Intestinal Suckling-to-Weaning Transition in Mice

10.21203/rs.3.rs-1040168/v1 ◽

2021 ◽

Author(s):

Eva Guilloteau ◽

Patrice COLL ◽

Zhuyi LU ◽

Madjid DJOUINA ◽

Mathieu CAZAUNAU ◽

...

Keyword(s):

Air Pollution ◽

Diversity Index ◽

Urban Air Pollution ◽

Female Offspring ◽

In Utero ◽

Urban Air ◽

Female Mice ◽

Junction Protein ◽

Pregnant Mice ◽

Pollution Event

Abstract Background Emerging data indicate that prenatal exposure to air pollution may lead to higher susceptibility to several non-communicable diseases. Limited research has been conducted due to difficulties in modelling realistic air pollution exposure. In this study, pregnant mice were exposed from gestational day 10 to 17 to an atmosphere representative of a 2013 pollution event in Beijing, China. Intestinal homeostasis and microbiota were assessed in both male and female offspring during the suckling-to-weaning transition. Results Sex-specific differences were observed in progeny of gestationally-exposed mice. In utero exposed males exhibited decreased villus and crypt length, vacuolation abnormalities, and lower levels of tight junction protein ZO-1 in ileum. They showed an upregulation of absorptive cell markers and a downregulation of neonatal markers in colon. Cecum of in utero exposed male mice also presented a deeply unbalanced inflammatory pattern. By contrast, in utero exposed female mice displayed less severe intestinal alterations, but included dysregulated expression of Lgr5 in colon, Tjp1 in cecum, and Epcam, Car2 and Sis in ileum. Moreover, exposed female mice showed dysbiosis characterized by a decreased weighted UniFrac β-diversity index, a higher abundance of Bacteroidales and Coriobacteriales orders, and a reduced Firmicutes/Bacteroidetes ratio. Conclusion Prenatal realistic modelling of an urban air pollution event induced sex-specific precocious alterations of structural and immune intestinal development in mice.

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